Role of Aldosterone and Mineralocorticoid Receptor in Cardiovascular Aging

Abstract

The mineralocorticoid receptor (MR) was originally identified as a regulator of blood pressure, able to modulate renal sodium handling in response to its principal ligand aldosterone. MR is expressed in several extra-renal tissues, including the heart, vasculature, and adipose tissue. More recent studies have shown that extra-renal MR plays a relevant role in the control of cardiovascular and metabolic functions and has recently been implicated in the pathophysiology of aging. MR activation promotes vasoconstriction and acts as a potent pro-fibrotic agent in cardiovascular remodeling. Aging is associated with increased arterial stiffness and vascular tone, and modifications of arterial structure and function are responsible for these alterations. MR activation contributes to increase blood pressure with aging by regulating myogenic tone, vasoconstriction, and vascular oxidative stress. Importantly, aging represents an important contributor to the increased prevalence of cardiometabolic syndrome. In the elderly, dysregulation of MR signaling is associated with hypertension, obesity, and diabetes, representing an important cause of increased cardiovascular risk. Clinical use of MR antagonists is limited by the adverse effects induced by MR blockade in the kidney, raising the risk of hyperkalaemia in older patients with reduced renal function. Therefore, there is an unmet need for the enhanced understanding of the role of MR in aging and for development of novel specific MR antagonists in the context of cardiovascular rehabilitation in the elderly, in order to reduce relevant side effects.

Corticosterone mediates a growth‐survival tradeoff for an amphibian exposed to increased salinity

“…Indirect actions of CORT, such as mobilizing energy to supply ATPase pumps, or direct actions could both occur. CORT and aldosterone are both regulated by the HPI axis and activate mineralocorticoid (MC) receptors that regulate fluids, electrolytes such as sodium, and blood pressure (Funder, 2005; Gorini et al, 2019). Larvae exposed only to salinity in our experiment had increased water retention similar to a previous study with wood frogs ( Rana sylvatica ; Hall et al, 2017).…”

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

“…Because MR is known as a receptor for aldosterone in various types of cells [ 21 , 22 ], we focused on the MR mediating the action of aldosterone in muscle cells. A binding affinity experiment using enzyme-linked immunosorbent assay (ELISA) indicated that the amount of aldosterone-associated MR increased as the amount of C2C12 myoblast lysate increased ( Fig.…”

Oxidative Stress and Vascular Damage in the Context of Obesity: The Hidden Guest

“…As already mentioned for Ang II, aldosterone through mineralocorticoid receptor (MR) activation plays a relevant role in the vascular damage associated with different pathological conditions included obesity [ 155 , 156 , 157 , 158 ]. In fact, an increase in aldosterone levels in the context of obesity has been also reported [ 124 , 156 , 159 , 160 , 161 ] even in the presence of a high salt-diet [ 159 ].…”